ABSTRACT The amygdala has been implicated in a number of neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD). This is likely because it is part of a system focused on detecting danger in the environment, processing cortical sensory input, and orchestrating subsequent responses. If this system becomes dysfunctional, inappropriate social behavior or anxiety may arise, as is observed in many, often debilitating, psychiatric disorders. Thus, treatment approaches may be facilitated by a precise understanding of the amygdala cellular composition and developmental trajectory that occurs across human lifespan. Considering impairments in social interaction and anxiety are key features of ASD, it is not surprising that the amygdala has been extensively implicated in ASD pathophysiology. The overarching objective of our research program is to reveal the cellular and molecular mechanisms underlying amygdala structure and function in typical human development and in ASD across the lifespan. In the first funding cycle of this research program, we discovered two phenomena through our studies of a large collection of human postmortem amygdala tissue samples. First, in neurotypical human brain development, the amygdala undergoes a substantial, protracted growth in both volume and in the number of mature neurons from youth well into adulthood. We hypothesize that this is attributable to a prolonged process of neuronal maturation in the basal and paralaminar nuclei, and that this protracted growth is critically important for normal social and emotional development. Second, in ASD brain development, the amygdala does not undergo the same age-related growth trajectory. Rather, the amygdala in ASD undergoes an aberrant, lifelong developmental time course that begins with premature volumetric enlargement and an excess number of mature neurons and synaptic spines in childhood. In fact, the number of mature neurons reaches adult levels by late childhood, suggesting that a preternatural neuronal maturation process is occurring in the amygdala basal and paralaminar nuclei. Dendrites of principal excitatory neurons in the amygdala of children with ASD also have an increase in spine density relative to neurotypical children, indicating altered neuronal synaptic communication. This increase is followed by a potentially degenerative cell loss as people with ASD age into adulthood. We have found that there is a steady decrease across age in the number of mature neurons in both the lateral and basal nucleus in adults with ASD relative to neurotypical adults. We hypothesize that hyperactivity and excitation in the amygdala, via an imbalance of excitatory to inhibitory (E:I) synaptic signaling, potentially contributes to anxiety, social impairments, and prospective neuron loss. We now move to the next phase of this research program, to identify specific neuronal properties and pathophysiological mechanisms that underlie the atypical amygdala cellular developmental trajectory in ASD that endures throughout the lifespan.